Implantable valvular prosthesis

ABSTRACT

The present invention relates to a medical device, and in particular, to a stent-based valve. The valve includes a radially expandable structural frame including an anchor structure having a first and a second open end, a connecting member having a first and a second end, and a cantilever valve strut having a first and a second end. The first end of the connecting member is attached to the second end of the anchor structure. The first end of the cantilever valve strut is cooperatively associated with the second end of the connecting member. The prosthetic valve further includes a biocompatible membrane assembly having a substantially tubular configuration about the longitudinal axis, with a first open and a second closed end. The first end of the membrane assembly is attached to the structural frame along the second end of the cantilever valve strut.

FIELD OF THE INVENTION

The present invention relates to a medical device, and more particularlyto a frame based unidirectional flow prosthetic valve, and the methodfor fabricating such valve.

BACKGROUND OF RELATED ART

The human body has numerous biological valves that control fluid flowthrough body lumens and vessels. For example the circulatory system hasvarious heart valves that allow the heart to act as a pump bycontrolling the flow of blood through the heart chambers, veins, andaorta. In addition, the venous system has numerous venous valves thathelp control the flow of blood back to the heart, particularly from thelower extremities.

These valves can become incompetent or damaged by disease, for example,phlebitis, injury, or the result of an inherited malformation. Heartvalves are subject to disorders, such as mitral stenosis, mitralregurgitation, aortic stenosis, aortic regurgitation, mitral valveprolapse and tricuspid stenosis. These disorder are potentially lifethreatening. Similarly, incompetent or damaged venous valves usuallyleak, allowing the blood to improperly flow back down-through veins awayfrom the heart (regurgitation reflux or retrograde blood flow). Bloodcan then stagnate in sections of certain veins, and in particular, theveins in the lower extremities. This stagnation of blood raises bloodpressure and dilates the veins and venous valves. The dilation of onevein may in turn disrupt the proper function of other venous valves in acascading manner, leading to chronic venous insufficiency.

Numerous therapies have been advanced to treat symptoms and to correctincompetent valves. Less invasive procedures include compression,elevation and wound care. However, these treatments tend to be somewhatexpensive and are not curative. Other procedures involve surgicalintervention to repair, reconstruct or replace the incompetent ordamaged valves, particularly heart valves.

Surgical procedures for incompetent or damaged venous valves includevalvuloplasty, transplantation, and transposition of veins. However,these surgical procedures provide somewhat limited results. The leafletsof some venous valves are generally thin, and once the valve becomesincompetent or destroyed, any repair provides only marginal relief.

As an alternative to surgical intervention, drug therapy to correctvalvular incompetence has been utilized. Currently, however, there areno effective drug therapies available.

Other means and methods for treating and/or correcting damaged orincompetent valves include utilizing xenograft valve transplantation(monocusp bovine pericardium), prosthetic/bioprosthetic heart valves andvascular grafts, and artificial venous valves. These means have all hadsomewhat limited results.

What is needed is an artificial endovascular (endoluminal) valve for thereplacement of incompetent biological human valves, particularly heartand venous valves. These valves may also find use in artificial heartsand artificial heart assist pumps used in conjunction with hearttransplants.

SUMMARY OF THE INVENTION

The present invention relates to a medical device, and in particular, toa stent-based valve. A prosthetic valve comprises a radially expandablestructural frame defining a longitudinal axis. The structural frameincludes an anchor structure having a first and a second open end, aconnecting member having a first and a second end, and a cantilevervalve strut having a first and a second end. The first end of theconnecting member is attached to the second end of the anchor structure.The first end of the cantilever valve strut is cooperatively associatedwith the second end of the connecting member. The prosthetic valvefurther includes a biocompatible membrane assembly having asubstantially tubular configuration about the longitudinal axis, with afirst open and a second closed end. The first end of the membraneassembly is attached to the structural frame along the second end of thecantilever valve strut.

In another embodiment of the invention, the prosthetic valve comprises aradially expandable anchor structure formed from a lattice ofinterconnected elements. The anchor has a substantially cylindricalconfiguration with a first and a second open end and a longitudinal axisdefining a longitudinal direction extending there between. A connectingmember and a cantilever valve strut, each having first and second ends,are also provided. The first end of the connecting member is attached tothe second end of the anchor. The first end of the cantilever valvestrut is cooperatively associated with the second end of the connectingmember. The prosthetic valve also includes a biocompatible membraneassembly having a substantially tubular configuration with a first openand a second closed end. The first end of the membrane assembly isattached to the cantilever valve strut along the second end of thecantilever valve strut.

In still another embodiment of the present invention, the prostheticvalve comprises a radially expandable anchor structure formed from alattice of interconnected elements. The anchor structure has asubstantially cylindrical configuration with a first and a second openend and a longitudinal axis defining a longitudinal direction extendingthere between. A collar is provided and located proximal to the radiallyexpandable anchor. At least one connecting member having a first and asecond end is provided such that the first end of the connecting memberis attached to the second end of the anchor and the second end of theconnecting member is attached to the proximal collar. A cantilever valvestrut is also provided. The cantilever valve strut has a first and asecond end; the first end of the cantilever valve strut is attached tothe proximal collar. The cantilever valve strut extends in a distaldirection substantially parallel to the longitudinal axis. Theprosthetic valve further comprises a biocompatible membrane assemblyhaving a substantially tubular configuration with a first open and asecond closed end. The first end of the membrane assembly is attached tothe cantilever valve strut along the second end of the cantilever valvestrut.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a perspective view of a prosthetic venous valve in thedeployed state according to one embodiment of the present invention.

FIG. 1B shows a perspective view of a prosthetic venous valve, having agraft cover, in the deployed state according to one embodiment of thepresent invention.

FIG. 2A shows a perspective view of the prosthetic venous valvestructural frame in the deployed state according to one embodiment ofthe present invention.

FIG. 2B shows a perspective view of the prosthetic venous valvestructural frame wherein the cantilever valve struts extend from theproximal collar in a proximal direction before looping back in a distaldirection according to one embodiment of the present invention.

FIG. 2C shows a perspective view of the prosthetic venous valvestructural frame having helical connecting members according to oneembodiment of the present invention.

FIG. 2D shows a perspective view of the prosthetic venous valvestructural frame having a sinusoidal cantilever valve strut assemblyaccording to one embodiment of the present invention.

FIG. 2E shows a perspective view of the prosthetic venous valvestructural frame having a helical valve strut assembly according to oneembodiment of the present invention.

FIG. 2F shows a perspective view of the prosthetic venous valvestructural frame having a proximal centering mechanism in the deployedstate according to one embodiment of the present invention.

FIG. 2G shows a perspective view of the prosthetic venous valvestructural frame having a distal and proximal anchor mechanism accordingto one embodiment of the present invention.

FIG. 3A shows a perspective view of the distal stent anchor having aplurality of hoop structures according to one embodiment of the presentinvention.

FIG. 3B shows a close-up perspective view of a loop member from theanchor having inner and outer radii according to one embodiment of thepresent invention.

FIG. 3C illustrates a single hoop anchor having three connecting membersconnected to the proximal end of the distal anchor at the outer radii ofthe inflection point of the loop members.

FIG. 3D illustrates a single hoop anchor having three connecting membersconnected to the proximal end of the distal anchor at the inner radii ofthe inflection point of the loop members.

FIG. 3E illustrates a single hoop anchor having three connecting membersconnected to the proximal end of the distal anchor along the strutmembers connecting the loop members.

FIG. 4A is a perspective view illustrating one embodiment of thedeployed prosthetic venous valve assembly in the open position.

FIG. 4B is a section view illustrating one embodiment of the deployedprosthetic venous valve assembly in the open position.

FIG. 5A is a perspective view illustrating one embodiment of thedeployed prosthetic venous valve assembly in the closed position.

FIG. 5B is a section view illustrating one embodiment of the deployedprosthetic venous valve assembly in the closed position.

FIG. 6A is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 6B is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 6C is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 6D is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The stent-based valves of the present invention provide a method forovercoming the difficulties associated with the treatment of valveinsufficiency. Although stent based venous valves are disclosed toillustrate one embodiment of the present invention, one of ordinaryskill in the art would understand that the disclosed invention can beequally applied to other locations and lumens in the body, such as, forexample, coronary, vascular, non-vascular and peripheral vessels, ducts,and the like, including but not limited to cardiac valves, venousvalves, valves in the esophagus and at the stomach, valves in the ureterand/or the vesica, valves in the biliary passages, valves in thelymphatic system and valves in the intestines.

In accordance with one aspect of the present invention, the prostheticvalve is designed to be percutaneously delivered through a body lumen toa target site by a delivery catheter. The target site may be, forexample, a location in the venous system adjacent to an insufficientvenous valve. Once deployed the prosthetic venous valve functions toassist or replace the incompetent or damaged natural valve by allowingnormal blood flow (antegrade blood flow) and preventing or reducingbackflow (retrograde blood flow).

A perspective view of a prosthetic venous valve in the deployed(expanded) state according to one embodiment of the present invention isshown in FIG. 1A. The prosthetic venous valve 100 comprises a structuralframe 101 and a biocompatible membrane assembly 102. The membraneassembly 102 is a thin-walled biocompatible material formed into a tubewith a closed end. Exemplary configurations of a closed end tube wouldinclude a tubular cup or cone shape, however one of skill in the artwould understand that other configurations could also be used.

The prosthetic venous vale 100 may also have a cover or graft materialcovering all or part of the structural frame 101. FIG. 1B shows aprosthetic valve 100 having a graft cover 109 according to anotherembodiment of the present invention. The graft 109 may be a biologicalmaterial, such as a vein or small intestine submucosa (SIS) formed intoa tube, but is preferably a synthetic material such as a polymer, forexample an elastic or elastomeric polymer, including a fluoropolymer,fluoroelastomer, Polytetrafluoroethylene (PTFE), or a bioabsorbablematerial. The graft material seals off the vessel wall, e.g. inperforations and ruptures, but also in aneurysms, dissections andfistulas. The graft material may also prohibit or limit vessel walltissue from protruding through the structural frame, occluding thevessel and/or inhibiting the operation of the membrane assembly 102.

For clarity, a perspective view of the prosthetic venous valve 100structural frame 101 according to one embodiment of the presentinvention is shown in FIG. 2A. The structural frame 101 consists of ananchor structure 104 connected by at least one connecting member 105 toa proximal collar 108. In a preferred embodiment, at least twoconnecting members 105 are utilized. By way of example, the embodimentillustrated in FIG. 2A shows four connecting members 105.

One or more cantilever valve struts 107 extend from the proximal collar108 in a distal (downstream) direction substantially parallel to thestructural frame 101 longitudinal axis 106. The cantilever valve struts107 are attached to the biocompatible membrane assembly 102 (not shownin FIG. 2A) and further support the assembly in the open and closedpositions. The proximal collar 108 serves as a connection point betweenthe one or move valve strut members 107 and the one or more connectingmembers 105.

In another embodiment of the invention illustrated in FIG. 2B, thecantilever valve struts 107 extend from the proximal collar 108 in aproximal direction before looping back in a distal directionsubstantially parallel to the structural frame 101 longitudinal axis106. As disclosed in FIG. 2A, the cantilever valve struts 107 areattached to the biocompatible membrane assembly 102 (not shown in FIG.2A or 2B) and further support the assembly in the open and closedpositions. This configuration allows the cantilever valve strut 107 tobe longer, increasing the flexibility of the struts 107 and helping toreduce the strains imposed in the structural frame 101 and/or membraneassembly 102.

The cantilever valve strut 107 illustrated in FIG. 2B has a loop end 112incorporated into the proximal end and a single branch distal end 113.The loop end 112 of the valve strut 107 is attached directly to theproximal end of the proximal collar 108, and has a semi-circularconfiguration, substantially symmetric about its center. Thisconfiguration allows the loop end 112 to effectively reverse thedirection of the cantilever valve strut 107 from a proximal direction,where it attaches to the proximal end of proximal collar 108, to adistal direction.

In a preferred embodiment, at least three cantilever valve struts 107are utilized. In the embodiment illustrated in FIGS. 2A and 2B, fourcantilever valve struts 107 are shown.

The number of cantilever valve struts 107 and connecting members 105illustrated are not meant to limit the scope of the invention. One ofskill in the art would understand that other quantities and combinationsof valve struts 107 and connecting members 105 could be used and stillaccomplish the general intent of the invention.

In addition, the structural frame 101, particularly the connectingmembers 105 and/or cantilever valve struts 107 may include radiopaquemarkers or marker bands attached or integrated thereto. The radiopaquemarkers are opaque to radiation, especially to X rays and MRI, allowingthe position of the structural frame 101 or its components to be viewed“in vivo”. FIG. 1 illustrates marker bands 103 along the cantilevervalve strut 107 members.

It should be noted that the terms proximal and distal are typically usedto connote a direction or position relative to a human body. Forexample, the proximal end of a bone may be used to reference the end ofthe bone that is closer to the center of the body. Conversely, the termdistal can be used to refer to the end of the bone farthest from thebody. In the vasculature, proximal and distal are sometimes used torefer to the flow of blood to the heart, or away from the heart,respectively. Since the prosthetic valves described in this inventioncan be used in many different body lumens, including both the arterialand venous system, the use of the terms proximal and distal in thisapplication are used to describe relative position in relation to thedirection of fluid flow. As used herein, the terms upstream anddownstream are relative to the normal direction of fluid flow (antegradeflow). By way of example, for venous valves, downstream connotes adirection of blood flow toward the heart. Accordingly, the use of theterm proximal in the present application describes an upstream member,section or relative position regardless of its orientation relative tothe body. The use of the term distal is used to describe a downstreammember, section or relative position regardless of its orientationrelative to the body. Similarly, the use of the terms proximal anddistal to connote a direction describe upstream (retrograde) ordownstream (antegrade) respectively.

In the embodiment illustrated in FIGS. 2A and 2B, the connecting members105 are substantially linear members; connecting the stent based distalanchor 104 and the proximal collar 108. Alternatively, the connectingmembers 105 may be twisted in a helical fashion as they extend betweenthe proximal collar 108 and the distal anchor 104. This alternateembodiment is illustrated in FIG. 2C. Specifically, the connectionpoints between the connecting members 105 and the distal anchor 104, andthe connecting members 105 and the proximal collar 108, are rotationallyphased 180 degrees from each other to provide the helical design.

Similarly, the cantilever valve struts 107 are illustrated as straightmembers, but may take on other configurations. By way of example, FIG.2D shows a structural frame 101 having sinusoidal cantilever valvestruts 107 while FIG. 2E shows a structural frame 101 having helicalcantilever valve struts 107. These various configurations may be used tochange the properties of the structural frame, for example, by providingmore flexibility in a particular plane or direction. Still otherconfigurations are possible as would be understood by one of skill inthe art.

The structural frame 101 could also include a secondary mechanism tocenter the proximal end of the frame in the body vessel or lumen. Thismechanism may also provide additional anchoring to the vessel wall tofurther stabilize the prosthetic valve 100.

FIG. 2F shows a centering mechanism 205 incorporated into the proximalend of the structural frame 101 according to one embodiment of thepresent invention. The centering mechanism 205 is comprised of one ormore legs 210 that extend in a substantially radial direction from thelongitudinal centerline 106 to the vessel wall (not shown). In theillustrated-embodiment, 4 legs 210 are shown for the purpose of example.The legs 210 terminate with a blunt end, such as the curved bendillustrated, to reduce the possibility of the leg end perforating thevessel wall. The opposite end of the leg 210 is attached to thestructural frame at or near the proximal collar 108. In the embodimentillustrated in FIG. 2F, the centering legs 210 are cut from the sametube as the remainder of the structural frame 101 such that thestructural frame 101, including legs 210, is a one piece unit.Alternatively, the centering legs 210 may be separate wire units andcrimped or suitably attached to the structural frame 101 at the proximalcollar 108. The leg 210 may include barbs 215 on or along the endportion to further anchor the structural frame 101 to the vessel wall.

The structural frame 101 may also include a second anchor mechanism 203,similar to anchor 104, as shown in FIG. 2G. Aside from providingadditional support and anchoring for the proximal end of the structuralframe 101, the proximal anchor 203 may also act as a centering mechanismto center the proximal end of the structural frame 101 in the vessel orlumen (not shown). The proximal anchor 203 may be attached directly tothe structural frame 101 at the proximal collar 108, or may be attachedto the proximal collar by connecting members 206 as shown in FIG. 2G. Asdisclosed above, the proximal anchor 203 and connecting members 206 maybe cut from the same tube as the remainder of the structural frame 101such that the structural frame 101, including the anchor 203 andconnecting members 206, is a one piece unit. Alternatively, the anchor203 and connecting members 206 may be separate units crimped or suitablyattached to the structural frame 101 at the proximal collar 108.

The materials for the structural frame 101 should exhibit excellentcorrosion resistance and biocompatibility. In addition, the materialcomprising the structural frame 101 should be sufficiently radiopaqueand create minimal artifacts during MRI.

The present invention contemplates deployment of the prosthetic venousvalve 100 by both assisted (mechanical) expansion, i.e. balloonexpansion, and self-expansion means. In embodiments where the prostheticvenous valve 100 is deployed by mechanical (balloon) expansion, thestructural frames 101 is made from materials that can be plasticallydeformed through the expansion of a mechanical assist device, such as bythe inflation of a catheter based balloon. When the balloon is deflated,the frame 101 remains substantially in the expanded shape. Accordingly,the ideal material has a low yield stress (to make the frame 101deformable at manageable balloon pressures), high elastic modulus (forminimal recoil), and is work hardened through expansion for highstrength. The most widely used material for balloon expandablestructures 101 is stainless steel, particularly 316L stainless steel.This material is particularly corrosion resistant with a low carboncontent and additions of molybdenum and niobium. Fully annealed,stainless steel is easily deformable.

Alternative materials for mechanically expandable structural frames 101that maintain similar characteristics to stainless steel includetantalum, platinum alloys, niobium alloys, and cobalt alloys. Inaddition other materials, such as polymers and bioabsorbable polymersmay be used for the structural frames 101.

Where the prosthetic venous valve 100 is self-expanding, the materialscomprising the structural frame 101 should exhibit large elasticstrains. A suitable material possessing this characteristic is Nitinol,a Nickel-Titanium alloy that can recover elastic deformations of up to10 percent. This unusually large elastic range is commonly known assuperelasticity.

The disclosure of various materials comprising the structural frameshould not be construed as limiting the scope of the invention. One ofordinary skill in the art would understand that other materialpossessing similar characteristics may also be used in the constructionof the prosthetic venous valve 100. For example, bioabsorbable polymers,such as polydioxanone may also be used. Bioabsorbable materials absorbinto the body after a period of time. The period of time for thestructural frame 101 to absorb may vary, but is typically sufficient toallow adequate tissue growth at the implant location to adhere to andanchor the biocompatible membrane 102.

The structural frame 101 may be fabricated using several differentmethods. Typically, the structural frame 101 is constructed from sheet,wire (round or flat) or tubing, but the method of fabrication generallydepends on the raw material form used.

The structural frame 101 can be formed from wire using convention wireforming techniques, such as coiling, braiding, or knitting. By weldingthe wire at specific locations a closed-cell structure may be created.This allows for continuous production, i.e. the components of thestructural frame 101, such as the anchors, to be cut to length from along wire mesh tube. The connecting members (i.e. 206, 105) may then beattached to the proximal and distal anchors. (i.e. 203, 104respectively), by welding or other suitable connecting means. When thisfabrication method is used, the proximal collar 108 may also be crimpedover the wire frame ends (i.e. connecting members, cantilever struts,and/or centering legs) to connect the individual members together.Alternatively, the wire ends may be attached to the proximal collar 108by welding or other suitable connecting means.

Alternatively, some or all of the complete structural frame 101 may becut from a solid wall tube or sheet of material. Laser cutting,water-jet cutting and photochemical etching are all methods that can beemployed to form the structural frame 101 from sheet and tube stock asare known in the art.

Referring to FIG. 2A for example, the structural frame 101 (includingthe distal anchor 104, connecting members 105, cantilever valve struts107 and proximal collar 108) may all be cut from a solid tubeeliminating the need for welding or mechanically attaching individualcomponents together. In this embodiment, the proximal collar 108 shownis the actual solid wall tube (and remains in the pre-cut, pre-expansionsize), while the remainder of the components comprising the structuralframe 101 are shown in the expanded (deployed) position. As one of skillin the art would understand, the proximal collar 108 serves as a commontermination point for the cantilever valve struts 107 and connectingmembers 105.

In other embodiments, the proximal anchor 203 or centering legs 210 maysimilarly be cut from the same solid wall tube as the remainder of thestructural frame 101.

Alternatively, the connecting members 105 and cantilever valve struts107 may be separate loose components, and tied to each other by theproximal collar 108. In this configuration, the proximal collar 108 actsas a connection point to connect or crimp down and hold the loosemembers in place. In other embodiments disclosed above, the centeringlegs 210, connecting members 206 and/or proximal anchor 203 may also befabricated separate from the other structural frame 101 components, andsimilarly attached or crimped in place at the proximal collar 108.

As discussed above, the disclosure of various methods for constructingthe structural frame 101 should not be construed as limiting the scopeof the invention. One of ordinary skill in the art would understand thatother construction methods may be employed to form the structural frame101 of the prosthetic venous valve 100.

In one embodiment of the invention, the anchor 104 (and in otherparticular embodiments, proximal anchor 203) are stent-based structures.This configuration facilitates the percutaneous delivery of theprosthetic venous valve 100 through the vascular system in a compressedstate. Once properly located, the stent-based venous valve 100 may bedeployed to the expanded state.

A perspective views of a typical stent-based anchor in the expanded(deployed) state is shown in FIG. 3A. Although stent anchor 104incorporating a plurality of hoop structures (306A through 306D) isshown in the illustrated embodiment, each stent anchor may utilize asingle hoop structure.

The distal stent anchor 104 (and in some embodiments proximal stentanchor 203) is comprised of a tubular configuration of structuralelements having proximal and distal open ends and defining thelongitudinal axis 106 extending therebetween. The stent anchor 104 has afirst diameter (not shown) for insertion into a patient and navigationthrough the vessels, and a second diameter D2 for deployment into thetarget area of a vessel, with the second diameter being greater than thefirst diameter. The stent anchor 104, and thus the stent based venousvalve 100, may be either a mechanical (balloon) or self-expanding stentbased structure.

The stent anchor 104 comprises at least one hoop structure 306 (306Athrough 306D are shown) extending between the proximal and distal ends.The hoop structure 306 includes a plurality of longitudinally arrangedstrut members 308 and a plurality of loop members 310 connectingadjacent struts 308. Adjacent struts 308 are connected at opposite endsin a substantially S or Z shaped pattern so as to form a plurality ofcells. The plurality of loops 310 have a substantially semi-circularconfiguration, having an inter radii 312 and outer radii 314, and aresubstantially symmetric about their centers. The inner and outer radii312, 314 respectively, are shown in a close-up perspective viewillustrated in FIG. 3B.

In the illustrated embodiment, the distal stent anchor 104 comprises aplurality of bridge members 314 that connect adjacent hoops 306A through306D. Each bridge member 314 comprises two ends 316A, 316B. One end316A, 316B of each bridge 314 is attached to one loop on one hoop. Usinghoop sections 306C and 306D for example, each bridge member 314 isconnected at end 316A to loop 310 on hoop section 306C at a point 320.Similarly, the opposite end 316B of each bridge member 314 is connectedto loop 310 on hoop sections 306D at a point 321.

As described earlier, although a Z or S shaped pattern stent anchor isshown for the purpose of example, the illustration is not to beconstrued as limiting the scope of the invention. One of ordinary skillin the art would understand that other stent geometries may be used.

The connecting member 105 may be connected to the distal anchor 104 atvarious points along the structure. As illustrated in FIG. 3A, theconnecting members 105 are connected to the proximal end of the distalanchor 104 at the inflection point of the loop members 310, particularlyat the outer radii 314 of the inflection point of loop members 310.Similarly, FIG. 3C illustrates a single hoop anchor 104 having threeconnecting members 105 connected to the proximal end of the distalanchor 104 at the outer radii 314 of the inflection point of loopmembers 310.

Preferably the connecting members 105 are connected to the inflectionpoint of loop members 310 at evenly spaced intervals along thecircumference of the tubular anchor 104. This configuration facilitatesthe radial expansion of the prosthetic valve from the collapsed(delivered) state to the expanded (deployed) state, and provides asubstantially symmetrical valve configuration.

Alternatively, the connecting members 105 may be connected to theproximal end of the distal anchor 104 at the inner radii 312 of theinflection point of loop member 310. This configuration is illustratedin FIG. 3D. FIG. 3D also illustrates a partial perspective view of thestructural frame 101 having a single hoop structure 306 and threeconnecting members.

In still a further embodiment, the connecting members 105 may beconnected along the strut members 308 of the distal anchor 104 as shownin FIG. 3E.

In any of the above described configurations, the connections betweenthe connecting members 105 and the anchor 104 may be made at everyinflection point around the circumference of the structure; oralternatively, at a subset of the inflection points around thecircumference of the structure. In other words, connected inflectionpoints alternate with unconnected inflection points in some definedpattern.

The distal anchor 104 secures the prosthetic valve 100 to the insidewall of a body vessel such as a vein, and provide anchor points for theconnecting members 105. Once deployed in the desired location, theanchor 104 will expand to an outside diameter slightly larger that theinside diameter of the native vessel (not shown) and remainsubstantially rigid in place, anchoring the valve assembly to thevessel. The connecting members 105 preferably have an inferior radialstiffness, and will conform much more closely to the native diameter ofthe vessel, facilitating the operation and stability of the prostheticvalve 100.

The stent anchor may also have spurs or barbs (not shown) protrudingfrom its proximal or distal end to further assist anchoring theprosthetic valve.

The membrane assembly 102 is formed from a flexible membrane-likebiocompatible material shaped into a tubular structure with a closedend. Exemplary embodiments would include a cup or cone shaped tube. Theflexible membrane may be elastic, semi-elastic or display little or noelasticity. One of skill in the art would appreciate that there are manydifferent methods, some known in the art, which may be employed tomanufacture the membrane assembly 102 from this material.

The biocompatible material may be a biological material, such as a veinor small intestine submucosa (SIS) formed into a cup or pocket, but ispreferably a synthetic material such as a polymer, for example anelastic or elastomeric polymer, including a fluoropolymer,fluoroelastomer, or a bioabsorbable material, such as a bioabsorbablepolymer or bioabsorbable elastomer. Bioabsorbable materials may allowcells to grow and form a tissue membrane (or valve flaps) over thebioabsorbable membrane. The bioabsorbable membrane then absorbs into thebody, leaving the tissue membrane and/or flaps in place to act as a newnatural tissue valve.

The membrane material may also be made from other synthetics, such asthin metallic materials or membranes.

The membrane must be strong enough to resist tearing under normal use,yet thin enough to provide the necessary flexibility that allows thebiocompatible membrane assembly 102 to open and close satisfactorily. Toachieve the necessary flexibility and strength of the membrane assembly102, the synthetic material may be, for example, reinforced with afiber, such as an electrostatically spun (ESS) fiber, or formed from aporous foam, such as ePTFE, or a mesh.

Particular ESS fibers suitable for the spinning process includefluoropolymers, such as a crystalline fluoropolymer with an 85/15%(weight/weight ratio) of vinylidene fluoride/hexafluoropropylene(VDF/HFP). Solvay Solef® 21508 and Kynarflex 2750-01 are two suchexamples. However, one of skill in the art would understand that anymaterial possessing the desired characteristics may be used, including,for example: bioabsorbable polymers, such as polyglycolic acid,polylactic acid, poly (paradioxanone), polycaprolactone, poly(trimethylenecarbonate) and their copolymers; and semicrystallinebioelastomers, such as 60/40%(weight/weight ratio) of polylacticacid/polycaprolactone (PLA/PCL), 65/35 (weight/weight ratio) ofpolyglycolic acid/polycaprolactone (PGA/PCL), or nonabsorbablesiliconized polyurethane, non-siliconized polyurethanes, siliconizedpolyureaurethane, including siliconized polyureaurethane end capped withsilicone or fluorine end groups, or natural polymers in combinationthereof. It should be noted that poly(trimethylenecarbonate) can not bespun as a homopolymer.

The ESS formed membrane assembly 102 may also be coated with a polymersolution, such as fluoroelastomer. The coating process may take placebefore the membrane assembly is attached to the cantilever valve struts107, or after the membrane assembly 102 and cantilever valve struts 107are assembled.

The coating process may act to encapsulate and attach at least a portionof the spun ESS reinforcement fiber to the cantilever valve strut 107assembly. It should be noted that in some embodiments of the invention,some movement between the membrane assembly 102 and the cantilever valvestrut 107 assembly is desired. Accordingly, not all of the ESS fiberspun cantilever valve strut 107 assembly may be coated.

The coating process may also remove some porosity of the membranematerial. However, it may be desirable to maintain some porosity inparticular embodiments to promote biological cell grown on and withinthe membrane tubular structure.

The coating solution preferably comprises a polymer put into solutionwith a solvent. As the solvent evaporates, the polymer comes out ofsolution forming the coating layer. Accordingly, for the process to workproperly, the solvent used in the coating solution should not dissolveor alter the ESS fibers being coated. By way of example, a coatingsolution of 60/40% VDF/HFP in methanol (methanol being the solvent) hasbeen found to be a suitable solution for coating an ESS fiber comprisedof 85/15% VDF/HFP.

In one embodiment of the invention, the polymer comprising the coatingis Daikin's Dai-El G701BP, which is a 60/40% VDF/HFP. In addition,Daikin's Dai-El T630, a thermoplastic elastomer based on vinylidenefluoride/hexafluoropropylene/tetrafluoroethylene (VDF/HFP/TFE) can alsobe used. Again, one of ordinary skill in the art would understand thatother materials having suitable characteristics may be used for thecoating, for example, other polymers, such as siliconized polyurethane,including Polymer Technology Group's Pursil, Carbosil, Purspan andPurspan F.

In another embodiment the membrane assembly is made from amicro-cellular foam or porous material, such as, for example an ePTFEmembrane.

In this embodiment, the membrane assembly 102 is fabricated from apolymer material that can be processed such that it exhibits an expandedcellular structure, preferably expanded Polytetrafluoroethylene (ePTFE).The ePTFE tubing is made by expanding Polytetrafluoroethylene (PTFE)tubing, under controlled conditions, as is well known in the art. Thisprocess alters the physical properties that make it satisfactory for usein medical devices. However, one of ordinary skill in the art wouldunderstand that other materials that possess the necessarycharacteristics could also be used.

The micro-cellular foam or porous material (preferably expandedPolytetrafluoroethylene (ePTFE)) may be coated with a polymer. Thepolymer can be coated on the inside or outside surface of the ePTFEtube. Alternatively, the polymer may be coated on the inside and outsideof the ePTFE tube.

In a preferred embodiment of the invention, the polymer comprising thecoating includes Daikin's Dai-El T630, a thermoplastic elastomer basedon vinylidene fluoride/hexafluoropropylene/tetrafluoroethylene(VDF/HFP/TFE) and blends thereof. Again, one of ordinary skill in theart would understand that other materials having suitablecharacteristics may be used for the coating, for example, otherpolymers, such as siliconized polyurethanes and blends thereof,including Polymer Technology Group's Pursil, Carbosil, Purspan andPurspan F.

The membrane assembly 102 formed from the micro-cellular foam or porousmembrane may also be coated with a fluoroelastomer. In one embodiment ofthe invention, the coating is Daikin G701BP, which is a 60/40% VDF/HFP.Again, one of ordinary skill in the art would understand that othermaterials having suitable characteristics might be used for the coating,for example, other polymers, such as siliconized polyurethane.

The coating process may take place before the membrane assembly isattached to the cantilever valve struts 107, or after the membraneassembly 102 and cantilever valve struts 107 are assembled. The coatingprocess may act to encapsulate and attach at least a portion of themicro-cellular foam or porous membrane tube to the cantilever valvestrut 107 assembly.

Some post processing of the membrane assembly 102 may also take place toachieve particular desired characteristics or configurations. This mayincludes creating the final closed cup or cone shape of the membraneassembly 102 if needed. In addition, post processing may change thecharacteristics of the membrane assembly 102 by thickening or thinningthe membrane in particular locations. Thickening the membrane may addrigidity and reinforcement to a particular area. Thinning the membranemay make the membrane more pliable, which is a desirable characteristic.Still other post processing procedures may change the physical shape ofthe membrane assembly 102, for example, by forming loop collars (such asloop collars 605 in FIGS. 6A through 6C) along the distal edge ofmembrane assembly 102.

The thickness of the synthetic valve membrane assembly 102 is dependenton the size, type and location of the prosthetic valve. For venousvalves applications a polymeric membrane assembly 102 having a thicknessof between 12 μm and 100 μm and preferably between 25 μm and 50 μm hasbeen found to be acceptable.

In one embodiment of the invention, the membrane assembly 102 is placedon the inside of the cantilever valve struts 107. However, in otherembodiments, the membrane assembly may be placed over the cantilevervalve struts 107.

FIGS. 4A and 4B are perspective and section views, respectively,illustrating one embodiment of the expanded (deployed) prosthetic venousvalve assembly 100 in the open position. In this embodiment, the termopen means that the prosthetic venous valve 100 is configured to allowantegrade blood flow 400 to pass through the valve. To accomplish this,the membrane assembly 102 is in a substantially collapsed position.

The flexible membrane like biocompatible material is formed into atubular cup or cone (membrane assembly 102) and suitably attached to thecantilever valve struts 107 of the structural frame 101. The membraneassembly 102 has a first (distal) and second (proximal) ends 401, 402respectively.

The first end 401 of the membrane assembly 102 is located at the distalend of the cantilever valve strut 107 near the proximal end of thedistal anchor 104. The membrane assembly extends proximally along thecantilever valve strut 107 and terminates at the second end 402 with aclosed cup or cone end.

The illustrated embodiment shows a valve having a single cone or cup,and may be considered a monocusp design. However, other configurationsusing more than a single cup or cone are also contemplated by thepresent invention.

During retrograde flow, blood passes the leading edge along the firstend 401 of the membrane assembly 102 and enters the membrane assembly102 “cup”. The cup quickly fills with the retrograde flowing blood,expanding the cup and opening the membrane assembly. As the membraneassembly 102 opens, the first end 401 is forced out toward vessel wall,substantially occluding the vessel and thus reducing retrograde flowthrough the valve. In a preferred embodiment, the membrane assembly 102will expand to a sufficient diameter to substantially seal against theinner vessel wall. FIGS. 5A and 5B show perspective and section views,respectively, illustrating one embodiment of the expanded (deployed)prosthetic venous valve assembly 100 in the closed position. As the termis used herein, closed means that the prosthetic venous valve 100 isconfigured to substantially prohibit retrograde blood flow 410 to passthrough the valve. To accomplish this, the membrane assembly 102 is inan expanded position, substantially occluding the vessel.

In a preferred embodiment of the invention, the membrane assembly 102 isnormally configured in the open position (membrane assembly 102substantially collapsed), and only moves to the closed position(membrane assembly 102 substantially expanded) upon retrograde bloodflow. This configuration minimizes interference with blood flow(minimized occlusion) and reduces turbulence at and through the valve.The cantilever valve struts 107 in this embodiment have an inferiorradial stiffness, and provide a natural bias against the movement of themembrane assembly 102 to the closed position. This bias assists thevalve membrane assembly 102 when returning to the open position.

Depending on the application, it may also be desirable for the biastowards opening the prosthetic valve 100 (collapsing the membraneassembly 102) be sufficiently high to commence collapsing the membraneassembly 102 before antegrade blood flow begins, i.e. during a point intime when the blood flow is stagnant (there is neither antegrade norretrograde blood flow), or when minimal retrograde flow is experienced.

In other applications, it may be desirable to have the valve assembly100 normally configured in the closed position (membrane assembly 102 inthe expanded position), biased closed, and only open upon antegradeflow.

As earlier described, the membrane assembly 102 is made from a flexiblemembrane-like biocompatible material. The membrane assembly 102 can bewoven, non-woven (such as electrostatic spinning), mesh, knitted, filmor porous film (such as foam).

The membrane assembly 102 may be fixedly attached to the structuralframe 101 (particularly cantilever valve strut 107) by many differentmethods, including attachment by means of a binder, heat, or chemicalbond, and/or attachment by mechanical means, such as welding orsuturing. In one embodiment, some of the membrane assembly 102, such asdistal end 401, is slideably attached to the cantilever valve strut 107.Allowing the distal end 401 to slide along the cantilever valve strut107 may allow or improve the opening and closing of the membraneassembly 102. The sliding movement may also assist the membrane assembly102 cup when filling and emptying.

In some applications, excessive sliding movement of the membraneassembly 102 is undesirable. In these embodiments, a limiting means maybe integrated into the prosthetic valve 100 to limit the slidingmovement of the membrane assembly 102. Examples of limiting means areshown in FIGS. 6A to 6C. In each embodiment a stop 600 (illustrated asstop 600A, 600B, and 600C in FIGS. 6A to 6C respectively) is integratedinto the cantilever valve strut 107. The membrane assembly 102 iswrapped around the cantilever valve strut 107 and bonded to itself toform a loop collar 605. Alternatively, the loop collar 605 may be aseparate biocompatible material wrapped around the cantilever valvestrut and bonded to the membrane assembly 102. This separate loop collar605 according to an alternate embodiment of the present invention isillustrated in FIG. 6D. The loop collar 605 must be sized to inhibit thedistal end 401 of the membrane assembly 102 from sliding past the stop600.

In FIG. 6A, the cantilever valve strut 107 has a thickened or “bulbous”section forming stop 600A. FIG. 6B illustrates an undulating stop 600Bconfiguration. Similarly, FIG. 6C shows the stop 600C configured as adouble bulbous section. It should be noted that the variousconfigurations illustrated in FIGS. 6A through 6C are exemplary. One ofordinary skill in the art would understand that other configurations ofstops may used.

It is important to note that the local delivery of drug/drugcombinations may be utilized to treat a wide variety of conditionsutilizing any number of medical devices, or to enhance the functionand/or life of the device. Medical devices that may benefit from thistreatment include, for example, the frame based unidirectional flowprosthetic implant subject of the present invention.

Accordingly, in addition to the embodiments described above, therapeuticor pharmaceutic agents may be added to any component of the deviceduring fabrication, including, for example, the ESS fiber, polymer orcoating solution, membrane tube, structural frame or inner and outermembrane, to treat any number of conditions. In addition, therapeutic orpharmaceutic agents may be applied to the device, such as in the form ofa drug or drug eluting layer, or surface treatment after the device hasbeen formed. In a preferred embodiment, the therapeutic and pharmaceuticagents may include any one or more of the following:antiproliferative/antimitotic agents including-natural products such asvinca alkaloids (i.e. vinblastine, vincristine, and vinorelbine),paclitaxel, epidipodophyllotoxins (i.e. etoposide, teniposide),antibiotics (dactinomycin (actinomycin D) daunorubicin, doxorubicin andidarubicin), anthracyclines, mitoxantrone, bleomycins, plicamycin(mithramycin) and mitomycin, enzymes (L-asparaginase which systemicallymetabolizes L-asparagine and deprives cells which do not have thecapacity to synthesize their own asparagine); antiplatelet agents suchas G(GP) ll_(b)/lll_(a) inhibitors and vitronectin receptor antagonists;antiproliferative/antimitotic alkylating agents such as nitrogenmustards (mechlorethamine, cyclophosphamide and analogs, melphalan,chlorambucil), ethylenimines and methylmelamines (hexamethylmelamine andthiotepa), alkyl sulfonates-busulfan, nirtosoureas (carmustine (BCNU)and analogs, streptozocin), trazenes—dacarbazinine (DTIC);antiproliferative/antimitotic antimetabolites such as folic acid analogs(methotrexate), pyrimidine analogs (fluorouracil, floxuridine, andcytarabine), purine analogs and related inhibitors (mercaptopurine,thioguanine, pentostatin and 2-chlorodeoxyadenosine {cladribine});platinum coordination complexes (cisplatin, carboplatin), procarbazine,hydroxyurea, mitotane, aminoglutethimide; hormones (i.e. estrogen);anticoagulants (heparin, synthetic heparin salts and other inhibitors ofthrombin); fibrinolytic agents (such as tissue plasminogen activator,streptokinase and urokinase), aspirin, dipyridamole, ticlopidine,clopidogrel, abciximab; antimigratory; antisecretory (breveldin);anti-inflammatory: such as adrenocortical steroids (cortisol, cortisone,fludrocortisone, prednisone, prednisolone, 6α-methylprednisolone,triamcinolone, betamethasone, and dexamethasone), non-steroidal agents(salicylic acid derivatives i.e. aspirin; para-aminophenol derivativesi.e. acetominophen; indole and indene acetic acids (indomethacin,sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac,and ketorolac), arylpropionic acids (ibuprofen and derivatives),anthranilic acids (mefenamic acid, and meclofenamic acid), enolic acids(piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone),nabumetone, gold compounds (auranofin, aurothioglucose, gold sodiumthiomalate); immunosuppressives: (cyclosporine, tacrolimus (FK-506),sirolimus (rapamycin), azathioprine, mycophenolate mofetil); angiogenicagents: vascular endothelial growth factor (VEGF), fibroblast growthfactor (FGF); angiotensin receptor blockers; nitric oxide donors;anti-sense oligionucleotides and combinations thereof; cell cycleinhibitors, mTOR inhibitors, and growth factor receptor signaltransduction kinase inhibitors; retenoids; cyclin/CDK inhibitors; HMGco-enzyme reductase inhibitors (statins); and protease inhibitors.

While a number of variations of the invention have been shown anddescribed in detail, other modifications and methods of use contemplatedwithin the scope of this invention will be readily apparent to those ofskill in the art based upon this disclosure. It is contemplated thatvarious combinations or subcombinations of the specific embodiments maybe made and still fall within the scope of the invention. For example,the embodiments variously shown to be prosthetic “venous valves” may bemodified to instead incorporate prosthetic “heart valves” and are alsocontemplated. Moreover, all assemblies described are believed usefulwhen modified to treat other vessels or lumens in the body, inparticular other regions of the body where fluid flow in a body vesselor lumen needs to be controlled or regulated. This may include, forexample, the coronary, vascular, non-vascular and peripheral vessels andducts. Accordingly, it should be understood that various applications,modifications and substitutions may be made of equivalents withoutdeparting from the spirit of the invention or the scope of the followingclaims.

The following claims are provided to illustrate examples of somebeneficial aspects of the subject matter disclosed herein which arewithin the scope of the present invention.

1. A prosthetic valve comprising: a radially expandable structural framedefining a longitudinal axis, including an anchor structure having firstand second open ends, a connecting member having first and second ends,the first end of the connecting member being attached to the second endof the anchor structure, and a cantilever valve strut having first andsecond ends, the first end of the cantilever valve strut beingcooperatively associated with the second end of the connecting member;and a biocompatible membrane assembly having a substantially tubularconfiguration about the longitudinal axis, with a first open and asecond closed end, the first end of the membrane assembly being attachedalong the second end of the cantilever valve strut.
 2. The prostheticvalve of claim 1 wherein the anchor structure is formed from a latticeof interconnected elements, and has a substantially cylindricalconfiguration about the longitudinal axis.
 3. The prosthetic valve ofclaim 1 wherein the structural frame comprises a material selected fromthe group consisting of stainless steel, tantalum, platinum alloys,niobium alloy, cobalt alloy, and nickel-titanium alloy.
 4. Theprosthetic valve of claim 1 wherein the structural frame comprises apolymer.
 5. The prosthetic valve of claim 1 wherein the biocompatiblemembrane assembly is formed from a flexible membrane-like material. 6.The prosthetic valve of claim 5 wherein the membrane-like material is abiological material.
 7. The prosthetic valve of claim 6 wherein thebiological material is a vein.
 8. The prosthetic valve of claim 5wherein the membrane-like material is a synthetic material.
 9. Theprosthetic valve of claim 8 wherein the synthetic material is anelastomeric polymer.
 10. The prosthetic valve of claim 8 wherein thesynthetic material is a bioabsorbable material.
 11. The prosthetic valveof claim 8 wherein the synthetic material further comprises areinforcement fiber.
 12. The prosthetic valve of claim 1 wherein atleast a portion of the structural frame is coated with an agent.
 13. Theprosthetic valve of claim 12 wherein the agent coating contains atherapeutic agent.
 14. The prosthetic valve of claim 12 wherein theagent coating contains a pharmaceutic agent.
 15. The prosthetic valve ofclaim 12 wherein the agent coating comprises an agent-eluting layer. 16.The prosthetic valve of claim 1 wherein at least a portion of themembrane assembly is coated with an agent.
 17. The prosthetic valve ofclaim 17 wherein the agent coating contains a therapeutic agent.
 18. Theprosthetic valve of claim 17 wherein the agent coating contains apharmaceutic agent.
 19. The prosthetic valve of claim 17 wherein theagent coating comprising an agent-eluting layer.
 20. The prostheticvalve of claim 1 wherein at least a portion of the membrane assembly isimpregnated with a therapeutic agent.
 21. The prosthetic valve of claim1 wherein at least a portion of the membrane assembly is impregnatedwith a pharmaceutic agent.
 22. The prosthetic valve of claim 1 whereinthe connecting member is a substantially straight member oriented in adirection substantially parallel to the longitudinal axis.
 23. Theprosthetic valve of claim 1 wherein the connecting member has asubstantially helical shape about the longitudinal axis.
 24. Theprosthetic valve of claim 1 wherein the cantilever valve strut is asubstantially straight member oriented in a direction substantiallyparallel to the longitudinal axis.
 25. The prosthetic valve of claim 1wherein the cantilever valve strut has a substantially helical shapeabout the longitudinal axis.
 26. The prosthetic valve of claim 1 whereinthe cantilever valve strut has a substantially sinusoidal shape orientedin a direction substantially parallel to the longitudinal axis.
 27. Theprosthetic valve of claim 1 wherein the tubular biocompatible membranehas a substantially constant diameter from the first to the second end.28. The prosthetic valve of claim 1 wherein the tubular biocompatiblemembrane has a substantially conical shape.
 29. The prosthetic valve ofclaim 1 wherein the structural frame further comprising a proximalcollar attached to the second end of the connecting member and first endof the cantilever valve strut.
 30. The prosthetic valve of claim 29wherein the structural frame further comprises a centering legcooperatively associated with the proximal collar.
 31. The prostheticvalve of claim 29 wherein the structural frame further comprises aproximal anchor cooperatively associated with the proximal collar.
 32. Aprosthetic valve comprising: a radially expandable anchor structureformed from a lattice of interconnected elements, and having asubstantially cylindrical configuration with a first and a second openend and a longitudinal axis defining a longitudinal direction extendingthere between; a connecting member having a first and a second end, thefirst end of the connecting member being attached to the second end ofthe anchor; a cantilever valve strut having a first and a second end,the first end of the cantilever valve strut being cooperativelyassociated with the second end of the connecting member; and abiocompatible membrane assembly having a substantially tubularconfiguration with a first open and a second closed end, the first endof the membrane assembly being attached to the cantilever valve strutalong the second end of the cantilever valve strut.
 33. A prostheticvalve comprising: a radially expandable anchor structure formed from alattice of interconnected elements, and having a substantiallycylindrical configuration with a first and a second open end and alongitudinal axis defining a longitudinal direction extending therebetween; a collar located proximal to the radially expandable anchor; aconnecting member having a first and a second end, the first end of theconnecting member being attached to the second end of the anchor and thesecond end of the connecting member being attached to the proximalcollar; a cantilever valve strut having a first and a second end, thefirst end of the cantilever valve strut being attached to the proximalcollar, the cantilever valve strut extending in a distal directionsubstantially parallel to the longitudinal axis; and a biocompatiblemembrane assembly having a substantially tubular configuration with afirst open and a second closed end, the first end of the membraneassembly being attached to the cantilever valve strut along the secondend of the cantilever valve strut.